Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2025 Apr 18;14(8):2810.
doi: 10.3390/jcm14082810.

Complement in Antibody-Mediated Rejection of the Kidney Graft: From Pathophysiology to Clinical Practice

Affiliations
Review

Complement in Antibody-Mediated Rejection of the Kidney Graft: From Pathophysiology to Clinical Practice

Bogdan Marian Sorohan et al. J Clin Med. .

Abstract

Antibody-mediated rejection (AMR) is a leading cause of kidney graft failure. Complement activation is involved in the AMR process. Our aim is to provide the current understanding of the pathophysiology related to complement-mediated injury in AMR, to present the current evidence regarding complement blockade in AMR management, and to point out emerging therapies and future directions in this area. The complement system plays an important role in the onset and progression of AMR. There is a balance between complement-dependent and -independent mechanisms in the development of rejection lesions. Classic and leptin pathways are involved in this process. C4d positivity is no longer a mandatory feature for AMR diagnosis but remains an independent predictor of negative outcomes. The current evidence regarding AMR treatment is limited. Terminal and proximal complement blockade has gained recognition in clinical practice. Eculizumab and C1 inhibitors are effective in the treatment of AMR as adjuvant therapies to the standard of care. The availability of novel complement inhibitors will lead to more effective and tailored treatment strategies.

Keywords: antibody; complement; kidney; pathophysiology; rejection; transplant; treatment.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Classical and lectin complement pathways activation in AMRs (HLAs—human leukocyte antibodies; DSAs—donor-specific antibodies; DAMPs—damage-associated molecular patterns; MASP—mannan-binding lectin serine protease; PRR—pattern recognition receptor; MBL—mannose-binding lectin; MAC—membrane attack complex).

References

    1. Axelrod D.A., Schnitzler M.A., Xiao H., Irish W., Tuttle-Newhall E., Chang S.-H., Kasiske B.L., Alhamad T., Lentine K.L. An Economic Assessment of Contemporary Kidney Transplant Practice. Am. J. Transplant. 2018;18:1168–1176. doi: 10.1111/ajt.14702. - DOI - PubMed
    1. Haas M., Mirocha J., Reinsmoen N.L., Vo A.A., Choi J., Kahwaji J.M., Peng A., Villicana R., Jordan S.C. Differences in Pathologic Features and Graft Outcomes in Antibody-Mediated Rejection of Renal Allografts Due to Persistent/Recurrent versus de Novo Donor-Specific Antibodies. Kidney Int. 2017;91:729–737. doi: 10.1016/j.kint.2016.10.040. - DOI - PubMed
    1. Sellarés J., De Freitas D.G., Mengel M., Reeve J., Einecke G., Sis B., Hidalgo L.G., Famulski K., Matas A., Halloran P.F. Understanding the Causes of Kidney Transplant Failure: The Dominant Role of Antibody-Mediated Rejection and Nonadherence. Am. J. Transplant. 2012;12:388–399. doi: 10.1111/j.1600-6143.2011.03840.x. - DOI - PubMed
    1. Arias-Cabrales C., Redondo-Pachón D., Pérez-Sáez M.J., Gimeno J., Sánchez-Güerri I., Bermejo S., Sierra A., Burballa C., Mir M., Crespo M., et al. Renal Graft Survival According to Banff 2013 Classification in Indication Biopsies. Nefrologia. 2016;36:660–666. doi: 10.1016/j.nefro.2016.05.018. - DOI - PubMed
    1. Aubert O., Loupy A., Hidalgo L., Duong van Huyen J.-P., Higgins S., Viglietti D., Jouven X., Glotz D., Legendre C., Lefaucheur C., et al. Antibody-Mediated Rejection Due to Preexisting versus De Novo Donor-Specific Antibodies in Kidney Allograft Recipients. J. Am. Soc. Nephrol. 2017;28:1912–1923. doi: 10.1681/ASN.2016070797. - DOI - PMC - PubMed

LinkOut - more resources